scholarly journals HOUT-19. THE SHORT-TERM OVERALL SURVIVAL ASSOCIATED WITH SINGLE- VS. MULTI-AGENT CHEMOTHERAPEUTIC REGIMENS FOR 1p/19q-CODELETED WHO GRADE III ANAPLASTIC OLIGODENDROGLIOMAS: A NATIONAL EVALUATION

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi116-vi116
Author(s):  
Mehdi Touat ◽  
Maya Harary ◽  
Vasileios Kavouridis ◽  
Timothy Smith ◽  
Bryan Iorgulescu
Keyword(s):  
Overall Survival ◽  
Logistic Regression ◽  
Cox Regression ◽  
Single Agent ◽  
First Line ◽  
Short Term ◽  
Who Grade ◽  
Multi Agent ◽  
Who Grade Iii ◽  
Grade Iii

Abstract INTRODUCTION Although diffuse gliomas of oligodendrocytic lineage demonstrate chemosensitivity, the survival outcomes associated with single- (i.e. temozolomide; TMZ) or multi-agent (i.e. PCV) chemotherapy regimens remain uncertain for anaplastic oligodendrogliomas (AO). METHODS Patients presenting between 2010–2016 with 1p/19q-codeleted WHO grade III AO were identified by ICD-O3 and site-specific factors from the National Cancer Database, which comprises >70% of cancers newly-diagnosed in the U.S. Predictors of receiving first-line single- vs. multi-agent chemotherapy were assessed by multivariable logistic regression. Overall survival (OS) was estimated by Kaplan-Meyer approaches and evaluated by multivariable Cox regression. RESULTS There were 952 patients with 1p/19q-codeleted WHO grade III AO and complete first-line chemotherapy data, with: 13.9% (n=132) no-, 75.0% (n=714) single-, and 11.1% (n=106) multi-agent chemotherapy. In logistic regression of chemotherapy-treated AOs, more recent diagnosis was associated with higher multi-agent (OR=1.48/year, 95%CI=1.25–1.74, p< 0.001) rates; otherwise there were no associations of single- vs. multi-agent chemotherapy with patient sex, age-at-diagnosis, race, insurance status (reference=privately insured), comorbidity index, tumor greatest dimension, tumor location (reference=frontal lobe) or crossing of midline, nor with radiotherapy or EOR (all p >0.05). Multi-agent usage rose from 3.6% in 2010 to 24.3% in 2016. Median follow-up was 34.9mos (IQR=18.8–54.8). The unadjusted 5yr-OS rate was 57.4% (95%CI=43.5–69.1) for no chemotherapy, 72.1% (95%CI=67.1–76.5) for single-agent, and 77.5% (95%CI=59.9–88.1) for multi-agent. Cox regression (adjusting for the above variables of radiotherapy and EOR, patient demographics, and tumor characteristics) demonstrated no significant OS difference between single- and multi-agent (HR=0.91, 95%CI=0.38–2.15, p=0.82) chemotherapy. CONCLUSIONS In a national database of AOs managed in the ‘real-world’ setting, there is increasing utilization of multi-agent (i.e. PCV) chemotherapy; but no significant difference in risk-adjusted short-term mortality (i.e. ~3-5yrs after diagnosis) between first-line multi- and single-agent (i.e. TMZ) chemotherapy. These findings provide preliminary data while we await the long-term PFS and OS results from the CODEL trial.

scholarly journals Short-term outcomes associated with temozolomide vs. PCV chemotherapy for 1p/19q-codeleted WHO grade III anaplastic oligodendrogliomas: a national evaluation

2020 ◽  
Author(s):  
Nayan Lamba ◽  
Malia McAvoy ◽  
Vasileios K. Kavouridis ◽  
Timothy R. Smith ◽  
Mehdi Touat ◽  
...  
Keyword(s):  
Cox Regression ◽  
Long Term Results ◽  
National Database ◽  
Newly Diagnosed ◽  
First Line ◽  
Short Term ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Pcv Chemotherapy ◽  
Grade Iii

AbstractPURPOSEThe optimal chemotherapy regimen between temozolomide (TMZ) and procarbazine, lomustine, and vincristine (PCV) remains uncertain for newly-diagnosed anaplastic oligodendroglioma (AO). We therefore addressed this question using a national database.METHODSPatients newly-diagnosed with 1p/19q-codeleted W.H.O. grade III AO between 2010-2016 were identified from the National Cancer Database. Predictors of receiving first-line single-agent TMZ vs. multi-agent PCV were assessed by multivariable logistic regression. Overall survival (OS) was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression.RESULTS1,360 AO patients were identified: 74.5% (n=1,013) treated with TMZ, 9.6% (n=131) with PCV, and 15.9% (n=216) with no chemotherapy in the first-line setting. In multivariable logistic analysis, PCV utilization increased from 2010 to 2016 (OR=1.38/year, 95%CI: 1.22-1.56, p<0.001) and was less commonly utilized in privately insured patients (OR=0.38 vs. uninsured, 95%CI: 0.15-0.97, p=0.04). In survival analyses (33.1% reached endpoint), there was no difference in unadjusted OS between TMZ (5yr-OS 60.1%, 95%CI: 55.9-64.1) and PCV (5yr-OS 61.1%, 95%CI: 45.6-73.5; p=0.42). There remained no OS difference between TMZ and PCV in the 75.9% (n=1,032) of AO patients that also received radiotherapy (p=0.51), in the Cox regression analysis adjusted by age, extent of resection, and radiotherapy (TMZ vs. PCV HR=1.31, 95%CI: 0.83-2.08, p=0.24), and in subgroup analyses that incorporate KPS or MGMT status.CONCLUSIONSIn a national database of AOs managed in the ‘real-world’ setting, there is no difference in the short-term mortality between first-line TMZ and PCV chemotherapy. These findings provide preliminary data while we await the long-term results from the CODEL trial.

Short-term outcomes associated with temozolomide or PCV chemotherapy for 1p/19q-codeleted WHO grade 3 oligodendrogliomas: a national evaluation

2022 ◽  
Author(s):  
Nayan Lamba ◽  
Malia McAvoy ◽  
Vasileios K Kavouridis ◽  
Timothy R Smith ◽  
Mehdi Touat ◽  
...  
Keyword(s):  
Cox Regression ◽  
Extent Of Resection ◽  
First Line ◽  
Short Term ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Pcv Chemotherapy ◽  
Grade 3 ◽  
National Analysis

Abstract Background The optimal chemotherapy regimen between temozolomide and procarbazine, lomustine, and vincristine (PCV) remains uncertain for W.H.O. grade 3 oligodendroglioma (Olig3) patients. We therefore investigated this question using national data. Methods Patients diagnosed with radiotherapy-treated 1p/19q-codeleted Olig3 between 2010-2018 were identified from the National Cancer Database. The OS associated with first-line single-agent temozolomide vs. multi-agent PCV was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression. Results 1,596 radiotherapy-treated 1p/19q-codeleted Olig3 patients were identified: 88.6% (n=1,414) treated with temozolomide and 11.4% (n=182) with PCV (from 5.4% in 2010 to 12.0% in 2018) in the first-line setting. The median follow-up was 35.5 months (interquartile range [IQR] 20.7-60.6 months) with 63.3% of patients alive at time of analysis. There was a significant difference in unadjusted OS between temozolomide (5yr-OS 58.9%, 95%CI: 55.6-62.0) and PCV (5yr-OS 65.1%, 95%CI: 54.8-73.5; p=0.04). However, a significant OS difference between temozolomide and PCV was not observed in the Cox regression analysis adjusted by age and extent of resection (PCV vs. temozolomide HR 0.81, 95%CI: 0.59-1.11, p=0.18). PCV was more frequently used for younger Olig3s, but otherwise was not associated with patient’s insurance status or care setting. Conclusions In a national analysis of Olig3s, first-line PCV chemotherapy was associated with a slightly improved unadjusted short-term OS compared to temozolomide; but not following adjustment by patient age and extent of resection. There has been an increase in PCV utilization since 2010. These findings provide preliminary data while we await the definitive results from the CODEL trial.

scholarly journals Analysis of Prognostic Factors of World Health Organization Grade Ⅲ Meningiomas

2020 ◽  
Vol 10 ◽  
Author(s):  
Weidong Tian ◽  
Jingdian Liu ◽  
Kai Zhao ◽  
Junwen Wang ◽  
Wei Jiang ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Postoperative Radiotherapy ◽  
World Health ◽  
Low Grade ◽  
Ki 67 ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

ObjectiveWHO grade III meningiomas are highly aggressive and lethal. However, there is a paucity of clinical information because of a low incidence rate, and little is known for prognostic factors. The aim of this work is to analyze clinical characteristics and prognosis in patients diagnosed as WHO grade III meningiomas.Methods36 patients with WHO grade III meningiomas were enrolled in this study. Data on gender, age, clinical presentation, preoperative Karnofsky Performance Status (KPS), histopathologic features, tumor size, location, radiologic findings, postoperative radiotherapy (RT), surgical treatment, and prognosis were retrospectively analyzed. Progression-free survival (PFS) and overall survival (OS) were evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were conducted by the Cox regression model.ResultsMedian PFS is 20 months and median OS is 36 months in 36 patients with WHO grade III meningiomas. Patients with secondary tumors which transformed from low grade meningomas had lower PFS (p=0.0014) compared with primary group. Multivariate analysis revealed that tumors location (PFS, p=0.016; OS, p=0.013), Ki-67 index (PFS, p=0.004; OS, p&lt;0.001) and postoperative radiotherapy (PFS, p=0.006; OS, p&lt;0.001) were associated with prognosis.ConclusionWHO grade III meningiomas which progressed from low grade meningiomas were more prone to have recurrences or progression. Tumors location and Ki-67 index can be employed to predict patient outcomes. Adjuvant radiotherapy after surgery can significantly improve patient prognosis.

PATH-32. EXTENT, PATTERN, AND PROGNOSTIC VALUE OF MGMT PROMOTOR METHYLATION: DOES IT DIFFER BETWEEN GLIOBLASTOMA AND IDH-WILDTYPE/TERT-MUTATED ASTROCYTOMA?

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi122-vi122
Author(s):  
Nico Teske ◽  
Philipp Karschnia ◽  
Jonathan Weller ◽  
Sebastian Siller ◽  
Mario M Dorostkar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Sanger Sequencing ◽  
Favourable Outcome ◽  
Who Grade ◽  
Cpg Sites ◽  
Specific Pcr ◽  
Grade Ii ◽  
Radio Chemotherapy ◽  
Who Grade Iii ◽  
Grade Iii

Abstract INTRODUCTION The cIMPACT-NOW update 6 introduced glioblastoma diagnosis based on the combination of IDH-wildtype (IDHwt) status and TERT promotor mutation (pTERTmut). In glioblastoma as defined by histopathology according to the WHO 2016 classification, MGMT promotor status is associated with outcome. Whether this is also true in glioblastoma defined by molecular markers is yet unclear. METHODS We searched the institutional database for patients with: 1.) glioblastoma defined by histopathology; and 2.) IDHwt astrocytoma with pTERTmut. MGMT promotor methylation was analysed using methylation-specific PCR and Sanger sequencing of CpG sites within the MGMT promotor region. RESULTS We identified 224 patients with glioblastoma diagnosed based on histopathology, and 71 patients with IDHwt astrocytoma with pTERTmut (32 astrocytomas WHO grade II and 39 astrocytomas WHO grade III). There was no difference in the number of MGMT methylated tumors between the two groups as determined per PCR, and also neither the number nor the pattern of methylated CpG sites differed as determined per Sanger sequencing. Progression-free (PFS) and overall survival (OS) was similar between the two groups. Surgery was associated with improved overall survival in IDHwt astrocytoma with pTERTmut. In patients treated with radiochemotherapy or radiotherapy, higher numbers of methylated CpG sites were associated with favourable outcome in both groups. CONCLUSION Extent and pattern of methylated CpG sites are similar in glioblastoma and IDHwt astrocytoma with pTERTmut. In both groups, higher numbers of methylated CpG sites are associated with favourable outcome when radio/chemotherapy is administered. Surgery may form the basis for favourable outcome.

The Newly Developed Modified BEACOPP-Regimen (BACOPP) Is Active and Feasible in Elderly Patients with Hodgkin Lymphoma: Results of a Phase II Study of the German Hodgkin Study Group (GHSG)

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2600-2600
Author(s):  
Horst Mueller ◽  
Lucia Nogova ◽  
Dennis A Eichenauer ◽  
Teresa Halbsguth ◽  
Hiltrud Nisters-Backes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Treatment Failure ◽  
Phase Ii Study ◽  
Final Analysis ◽  
Who Grade ◽  
Kaplan Meier ◽  
Advanced Stages ◽  
Who Grade Iii ◽  
Grade Iii

Abstract Background: Approximately 20% of patients diagnosed with Hodgkin lymphoma (HL) are more than 60 years of age. These elderly patients still have a poor prognosis, especially when presenting with advanced stages and higher age. The main reason is underdosing of treatment, which is due to reduced tolerability of chemotherapy and age-related comorbidities. In the GHSG experience, elderly patients in the HD9 trial did not profit from the BEACOPP regimen in terms of overall survival, though a better HL specific freedom from treatment failure was achieved as compared to COPP/ABVD. Thus, the GHSG has developed the BACOPP regimen (bleomycin, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone), in which etoposide was omitted to improve tolerability. Further modifications were a 1 week pretreatment phase with vincristine and prednisone, a limitation of vincristine in patients older than 65 years, an increase of the anthracyclines dose, and concomitant application of erythropoietin. Here we report on the final analysis of this multi-center phase II study for elderly patients. Methods: Between 2004 and 2005, 65 patients with HL in intermediate or advanced stages aged between 60 and 75 years were recruited. Treatment consisted of 6 cycles BACOPP in patients achieving a complete remission (CR) after 4 cycles or 8 cycles BACOPP in case of PR (partial remission) after 4 cycles. The primary endpoints were protocol adherence and response rates. Secondary endpoints included WHO grade III/IV toxicities, Kaplan Meier estimates of progression free survival (PFS), freedom from treatment failure (FFTF), and overall survival (OS). Results: Sixty patients (92%) were eligible for the final analysis. The majority of treatment courses (75%) were administered according to protocol. However, there was a tendency towards reduced dosing in cycles 5 to 8, especially for patients who had reached a CR after 4 cycles of BACOPP. In total, 51 patients showed CR/CRu (85%), 2 PR (3%) and 4 progression of disease (7%). Survival estimates and their 95% confidence intervals are shown in table 1. Table 1. Kaplan-Meier rates and 95% confidence intervals (CI) for FFTF, PFS and OS. time point rate (%) CI (95%) FFTF 12 months 73 61–84 24 months 67 55–79 PFS 12 months 75 64–86 24 months 68 56–80 OS 12 months 85 76–94 24 months 76 65–87 WHO grade III–IV toxicities were documented in 52 patients (87%). With a median observation time of 33 months, 18 deaths (30%) have been observed. Seven therapy associated fatal outcomes were documented. Conclusion: The new BACOPP regimen developed for elderly HL patients shows a high CR rate (85%). The FFTF rate at 2 years is within the range known from other schedules in this patient cohort. Overall, the regimen is feasible, but the therapy-associated death rate was high in our patient cohort. Thus, further studies and new approaches are still needed to substantially improve the outcome of elderly patients with early unfavorable or advanced stage HL.

scholarly journals NCOG-48. TRANSFORMATION FROM LOW GRADE MENINGIOMA AND PROGNOSTIC FACTORS FOR SHORTER TIME TO RECURRENCE OF WHO GRADE III MENINGIOMA DIAGNOSIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii140-ii140
Author(s):  
Jessica Chew ◽  
William Chen ◽  
Matthew S Susko ◽  
Harish N Vasudevan ◽  
Steve Braunstein ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rates ◽  
Unmet Need ◽  
Low Grade ◽  
Who Grade ◽  
Subsequent Transformation ◽  
Time To Recurrence ◽  
Who Grade Iii ◽  
Grade Iii

Abstract BACKGROUND WHO grade III meningiomas are rare, and clinical outcomes data are limited. To address this problem, we analyzed a single institution retrospective cohort of patients with WHO grade III meningiomas. METHODS Patients who underwent resection of WHO grade III meningiomas between 1983 and 2019 with available follow-up data were included. Treatment, local recurrence, and overall survival rates were obtained. Kaplan-Meier analysis, log rank tests, and Student’s t tests were used for statistical analyses. RESULTS Ninety consecutive patients met inclusion criteria. Median follow-up was 3.2 years (IQR: 1.2-7.9), median age was 58 years (IQR: 46-67). Twenty-three patients (26%) underwent resection alone, and 58 (64%) underwent resection with adjuvant radiotherapy. Fifty-one patients developed local recurrences, with median time to recurrence of 1.0 year (IQR: 0.6-2.9) and higher MIB-1 labeling index for tumors that recurred within 1 year (25% versus 17%, p=0.04). There was a median of 2 recurrences per patient (IQR: 1-3), with a median of 2 resections and 2 radiotherapy courses for initial and salvage treatments. Thirty-nine patients with recurrences died, with median overall survival of 3.7 years (IQR: 1.8-8.8). Thirty-seven patients (41%) had prior low grade meningioma diagnoses with subsequent transformation to grade III, including 6 (7%) with grade I, 16 (18%) with grade II, and 15 (17%) with unknown grade. There was a median of 1 low grade recurrence per patient (IQR: 0-3) before transformation to grade III, which occurred a median of 4.3 years (IQR: 2.4-9.9) after initial diagnosis. Prior low grade diagnosis was associated with shorter time to recurrence of WHO grade III meningioma (p=0.01), and worse overall survival (p=0.03). CONCLUSION Patients with WHO grade III meningioma have poor outcomes despite aggressive multimodal therapy, and there is an urgent, unmet need for new high grade meningioma treatments.

scholarly journals CTNI-29. CODEL: PHASE III TRIAL OF RT ALONE, RT PLUS TMZ, OR TMZ ALONE FOR NEWLY-DIAGNOSED, 1p/19q CODELETED ANAPLASTIC OLIGODENDROGLIOMA. ANALYSIS FROM THE INITIAL STUDY DESIGN. (NCCTG N0577, ALLIANCE)

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii48-ii49
Author(s):  
Kurt Jaeckle ◽  
Karla Ballman ◽  
Martin van den Bent ◽  
Caterina Giannini ◽  
Evanthia Galanis ◽  
...  
Keyword(s):  
Cox Regression ◽  
Initial Study ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Who Grade ◽  
Phase Iii Trial ◽  
Grade 3 ◽  
Who Grade Iii ◽  
Grade Iii

Abstract BACKGROUND The original 3-arm CODEL design included a radiotherapy (RT)-alone control arm, an RT plus temozolomide (TMZ) arm, and an exploratory TMZ-alone arm. We report the analysis involving patients treated per the initial design. METHODS Adults (18+ years) with newly-diagnosed 1p/19q codeleted WHO grade III oligodendroglioma were randomized to RT (5940 cGy) alone (Arm A); RT with concomitant and adjuvant TMZ (Arm B); or TMZ alone (Arm C). Primary endpoint was OS, Arm A vs. B. Secondary comparisons were performed for OS and PFS, comparing pooled RT arms with the TMZ-alone arm. RESULTS 36 patients were randomized equally to the three arms. At median follow-up of 7.5 years, 83.3% (10/12) TMZ-alone patients had progressed, versus 37.5% (9/24) patients on the RT arms. PFS was shorter in TMZ-alone patients compared to RT-treated patients (HR=3.12; 95% CI: 1.26, 7.69; p=0.014). Death from disease progression occurred in 3/12 (25%) of TMZ-alone patients and 4/24 (16.7%) of RT-treated patients. OS did not statistically differ between arms, although this comparison was underpowered. After adjustment for IDH status (mutated vs. wildtype) in a Cox regression model, with IDH status and RT treatment status as co-variables (Arm C vs pooled A and B), PFS remained shorter for patients not receiving RT (HR= 3.33; 95% CI: 1.31, 8.45; p=0.011), and OS differences remained non-significant ((HR = 2.78; 95% CI 0.58, 13.22, p=0.20). Grade 3+ adverse events occurred in 25%, 42% and 33% patients (Arms A, B and C, respectively). Neurocognitive assessments, comparing baseline and 3 month timepoints, showed no significant differences between arms. CONCLUSIONS TMZ-alone treated patients experienced significantly shorter PFS than patients treated on the pooled RT arms, which remained significant when adjusting for IDH status. CODEL has been redesigned to compare the efficacy and toxicity of RT+PCV versus RT+TMZ. Clinicaltrials.gov Identifier: NCT00887146. Support: U10CA180821, U10CA180882, https://acknowledgments.alliancefound.org.

Outcome and survival following primary and repeat surgery for World Health Organization Grade III meningiomas

2010 ◽  
Vol 113 (2) ◽  
pp. 202-209 ◽  
Author(s):  
Michael E. Sughrue ◽  
Nader Sanai ◽  
Gopal Shangari ◽  
Andrew T. Parsa ◽  
Mitchel S. Berger ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Data ◽  
World Health ◽  
Gross Total Resection ◽  
Total Resection ◽  
Repeat Surgery ◽  
Who Grade ◽  
Kaplan Meier ◽  
Who Grade Iii ◽  
Grade Iii

Object Despite an increased understanding of the biology of malignant meningioma tumor progression, there is a paucity of published clinical data on factors affecting outcomes following treatment for these lesions. The authors present the largest case series to date dealing with these tumors, providing analysis of 63 patients. Methods The authors identified all patients undergoing resection of WHO Grade III tumors at their institution over a 16-year period. They analyzed clinical data from these patients, and performed Kaplan-Meier and Cox regression analyses to determine the impact of different clinical characteristics and different treatment modalities on survival following initial and repeat surgery for these lesions. Results Sixty-three patients met inclusion criteria and were analyzed further. The median clinical follow-up time was 5 years (range 1–22 years). The 2-, 5-, and 10-year overall survival rates following initial operation were 82, 61, and 40%, respectively. Kaplan-Meier analysis demonstrated a marked survival benefit with repeat operation (53 vs 25 months, p = 0.02). Interestingly, patients treated with near-total resection experienced improved overall survival when compared with patients treated with gross-total resection at initial (p = 0.035) and repeat operations (p = 0.005). Twelve (19%) of 63 patients experienced significant neurological morbidity referable to the resection of their tumors. Conclusions Surgery is an effective treatment for WHO Grade III meningiomas at presentation and recurrence; however, aggressive attempts to achieve gross-total resection can be associated with significant neurological risk.

Bevacizumab for recurrent WHO grade III anaplastic glioma (AG).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2028-2028
Author(s):  
Anna Maria Delios ◽  
Cameron W Brennan ◽  
Jason T. Huse ◽  
Kara Colevas ◽  
Antonio Marcilio Padula Omuro
Keyword(s):  
Randomized Study ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Cytotoxic Agent ◽  
Molecular Characteristics ◽  
Who Grade ◽  
Who Grade Iii ◽  
Grade Iii

2028 Background: Salvage treatment with bevacizumab (BEV) has been increasingly used in grade III AG, but limited data are available, with conflicting results reported. Because of differences in molecular characteristics, angiogenesis mechanisms, growth rate and chemosensitivity, results observed in glioblastoma (GBM) treated with BEV may not apply to AG, and may differ between anaplastic astrocytomas (AA) and oligodendrogliomas (AO). Methods: IRB approved retrospective review of all pts with recurrent WHO grade III AG treated with BEV at MSKCC. Response and progression were determined by RANO criteria. Results: BEV was given to 39 pts with recurrent grade III AG (AA: 26; AO: 10; anaplastic oligoastrocytoma [AOA]: 3); median (med) age: 49 (range 20-75); med KPS: 80 (60-100). MGMT promoter methylation was determined in 17 pts (methylated 8, unmethylated 9). Amongst AO/AOA, 1p/19q co-deletion was present in 6 and absent in 5. IDH1/ IDH2 mutations were present in 3/5 tested tumors. Med time from diagnosis of AG to BEV treatment was 11.5m (3 – 112.5). The med number of previous recurrences was 1 (range 1-4). BEV was given as single agent to 16 pts and combined with a cytotoxic agent in 23. Objective response rate (ORR) was 41% (complete response: 5; partial: 11). The med progression-free survival (PFS) was 4.8m (6-m PFS: 35% [95% CI 20-50]). The med overall survival (OS) was 11.5 m (1y-OS: 45% [95% CI 29-61]). In pts achieving ORR, med OS was 13 m vs 4 m in pts with stable/progressive disease (P=0.02). Pts at first recurrence fared better than pts with more than one recurrence (med PFS: 6 vs 3.4 months, P=0.04). AO/AOA tended to fare worse than AA (med PFS 3 vs 5.5 m, P=0.07). There were no differences in PFS (P=0.8) or OS (P=0.4) between single agent vs BEV + cytotoxic agent. Toxicity included one grade 4 brain hemorrhage. Conclusions: In this relatively large series, BEV was associated with higher ORR and PFS as compared to historical controls, although improvements in those endpoints were of a lower magnitude than in GBM. While ORR predicted OS, improvements in OS were not apparent; results in AO were particularly disappointing. The use of BEV in this population requires reappraisal in a randomized study with adequate stratification for histology and number of previous recurrences.

scholarly journals A systematic review of treatment outcomes in pediatric patients with intracranial ependymomas

2013 ◽  
Vol 11 (6) ◽  
pp. 673-681 ◽  
Author(s):  
Tene A. Cage ◽  
Aaron J. Clark ◽  
Derick Aranda ◽  
Nalin Gupta ◽  
Peter P. Sun ◽  
...  
Keyword(s):  
Overall Survival ◽  
Pediatric Patients ◽  
Progression Free Survival ◽  
Tumor Location ◽  
Who Grade ◽  
Free Survival ◽  
Grade Ii ◽  
Infratentorial Tumors ◽  
Who Grade Iii ◽  
Grade Iii

Object Ependymoma is the third most common primary brain tumor in children. Tumors are classified according to the WHO pathological grading system. Prior studies have shown high levels of variability in patient outcomes within and across pathological grades. The authors reviewed the results from the published literature on intracranial ependymomas in children to describe clinical outcomes as they relate to treatment modality, associated mortality, and associated progression-free survival (PFS). Methods A search of English language peer-reviewed articles describing patients 18 years of age or younger with intracranial ependymomas yielded data on 182 patients. These patients had undergone treatment for ependymoma with 1 of 5 modalities: 1) gross-total resection (GTR), 2) GTR as well as external beam radiation therapy (EBRT), 3) subtotal resection (STR), 4) STR as well as EBRT, or 5) radiosurgery. Mortality and outcome data were analyzed for time to tumor progression in patients treated with 1 of these 5 treatment modalities. Results Of these 182 patients, 69% had supratentorial ependymomas and 31% presented with infratentorial lesions. Regardless of tumor location or pathological grade, STR was associated with the highest rates of mortality. In contrast, GTR was associated with the lowest rates of mortality, the best overall survival, and the longest PFS. Children with WHO Grade II ependymomas had lower mortality rates when treated more aggressively with GTR. However, patients with WHO Grade III tumors had slightly better survival outcomes after a less aggressive surgical debulking (STR+EBRT) when compared with GTR. Conclusions Mortality, PFS, and overall survival vary in pediatric patients with intracranial ependymomas. Pathological classification, tumor location, and method of treatment play a role in outcomes. In this study, GTR was associated with the best overall and PFS rates. Patients with WHO Grade II tumors had better overall survival after GTR+EBRT and better PFS after GTR alone. Patients with WHO Grade III tumors had better overall survival after STR+EBRT. Patients with infratentorial tumors had improved overall survival compared with those with supratentorial tumors. Progression-free survival was best in those patients with infratentorial tumors following STR+EBRT. Consideration of all of these factors is important when counseling families on treatment options.

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